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Trans-acting genetic variation affects the expression of adjacent genes

View ORCID ProfileKrisna Van Dyke, Gemechu Mekonnen, Chad L. Myers, View ORCID ProfileFrank W. Albert
doi: https://doi.org/10.1101/2020.10.05.327130
Krisna Van Dyke
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, U.S.A
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Gemechu Mekonnen
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, U.S.A
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Chad L. Myers
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, U.S.A
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Frank W. Albert
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, U.S.A
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  • ORCID record for Frank W. Albert
  • For correspondence: falbert@umn.edu
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Abstract

Gene expression differences among individuals are shaped by trans-acting expression quantitative trait loci (eQTLs). Most trans-eQTLs map to hotspot locations that influence many genes. The molecular mechanisms perturbed by hotspots are often assumed to involve “vertical” cascades of effects in pathways that can ultimately affect the expression of thousands of genes. Here, we report that trans-eQTLs can affect the expression of adjacent genes via “horizontal” mechanisms that extend along a chromosome. Genes affected by trans-eQTL hotspots in the yeast Saccharomyces cerevisiae were more likely to be located next to each other than expected by chance. These paired hotspot effects tended to occur at adjacent genes that show coexpression in response to genetic and environmental perturbations. Physical proximity and shared chromatin state, in addition to regulation of adjacent genes by similar transcription factors, were independently associated with paired hotspot effects. The effects of trans-eQTLs can spread among neighboring genes even when these genes do not share a common function. This phenomenon could result in unexpected connections between regulatory genetic variation and phenotypes.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/Krivand/Trans-acting-genetic-variation-affects-the-expression-of-adjacent-genes

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 07, 2020.
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Trans-acting genetic variation affects the expression of adjacent genes
Krisna Van Dyke, Gemechu Mekonnen, Chad L. Myers, Frank W. Albert
bioRxiv 2020.10.05.327130; doi: https://doi.org/10.1101/2020.10.05.327130
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Trans-acting genetic variation affects the expression of adjacent genes
Krisna Van Dyke, Gemechu Mekonnen, Chad L. Myers, Frank W. Albert
bioRxiv 2020.10.05.327130; doi: https://doi.org/10.1101/2020.10.05.327130

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